Studies on uteroglobin continues. During the past decade several proteins have been characterized as exerting an antiinflammatory effect via inhibition of phospholipase (PL) activity. These endogenous phospholipase inhibitors include (i) lipomodulin, a 40K protein isolated from glucocorticoid-treated rabbit neutrophils, (ii) macrocortin, a 15K protein isolated from glucocorticoid-treated rabbit macrophages, and (iii) renocortin isolated from glucocorticoid-treated rat renomedullary cells. It has been shown that these proteins prevent inflammation by inhibiting phospholipase A2 (PLA2), thereby blocking prostaglandin formation at a step proximal to arachidonic acid release. Since uteroglobin has been shown to be a progesterone-induced antiinflammatory protein in the uterus and corticosteroid-induced protein in the tracheobronchial epithelium of the rabbit, we investigated whether or not uteroglobin is also a phospholipase inhibitor. We found that uteroglobin inhibits PLA2 derived from porcine pancreas as well as from cultured mouse macrophages. A dose dependent inhibition of PLA2 by uteroglobin was observed with a maximum inhibition at a concentration of 20 MuM of this protein. We speculate that previously observed effects of uteroglobin, including its immunomodulatory, platelet aggregation inhibitory and uterine antimotility effects, could be explained by one central effect of uteroglobin, i.e., PLA-2 inhibition. In a related study we have reacently discovered that in the human, a protein similar to uteroglobin could be identified by radioimmunoassay, Western blot and HPLC. The human protein has so far been localized in human tracheobroncheal, uterine and prostatic epithelium by immunofluorescence. Further characterization of the protein, including its function, is now being investigated.